Stimulation of tumor necrosis factor receptor superfamily, member 25 (TNFRSF25) in vivo with its natural ligand TNFSF15 (also known as TL1A), facilitates selective proliferation of Treg in mice and suppression of immunopathology in allergic lung inflammation, allogeneic heart transplantation and HSV-1 mediated ocular inflammation. Progress in translating Treg therapy in humans has been slow, however, and thus far limited to ex vivo cell culture methodologies. Furthermore, such therapies must also be safe and avoid dangerous side effects, such as susceptibilities to inflammatory bowel disease (IBD). Prolonged stimulation with certain TNFRSF25 agonists have been known to cause harmful side effects in vivo, including, for example, increased inflammation in mouse models of asthma, inflammatory bowel disease and arthritis. Thus improved therapies that are safe and effective for Treg therapy in humans are needed.